The remodeling of bone is a dynamic process. Cells continuously lay down and resorb bone material. Bone homeostasis refers to the balance between bone formation and bone degradation. An imbalance in the activity of cells that lay down new bone (osteoblasts) and cells that resorb bone (osteoclasts) can result in serious, and sometimes fatal, disorders. Thus, imbalances in bone homeostasis are associated with a variety of adverse medical conditions.
Osteoporosis is a term used for a number of diseases of diverse etiology, all involving a reduction in the mass of bone per unit volume. Osteoporosis is the most common of the metabolic bone diseases. Twenty-five million people in the United States and more than two hundred million people worldwide are affected by osteoporosis. Osteoporosis is frequent among post-menopausal women and is an important cause of morbidity in the elderly. It commonly results in bone fractures, and death can be a frequent occurrence in the months following fractures, particularly those of the hip in elderly individuals.
Osteopetrosis is a disorder involving an increase in the mass of bone per unit volume. Its incidence is rare compared to osteoporosis, but it typically is life threatening. Despite having multiple causes, a defect in bone resorption is always the underlying mechanism. In many instances, the disorder is inherited as an autosomal recessive trait and involves abnormal osteoclast function. Bone marrow transplants from normal donors have been attempted to restore normal osteoclast precursor cells, but this therapy has shown only limited success. Present treatments for disorders of bone homeostasis are inadequate.
In view of the foregoing, a need exists to develop new and improved methods and compositions for treating disorders of bone homeostasis. Preferably such methods and compositions are based upon inhibiting the particular interactions between cell components which mediate the abnormal physiological effect, thereby minimizing harmful side effects that may be due to non-specific therapeutic approaches.